dc.contributor.author
Lemke, Oliver
dc.date.accessioned
2020-02-25T09:58:44Z
dc.date.available
2020-02-25T09:58:44Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/26738
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-26495
dc.description.abstract
The analysis of the structural and the dynamical behavior of biomolecules is very important to under- stand their biological function, stability or physico-chemical properties. In this thesis, it is highlighted how different theoretical methods to characterize the aforementioned structural and dynamical properties can be used and combined, to obtain kinetic information or to detect biomolecule-ligand interactions. The basis for most of the analyses, performed in the course of this work, are molecular dynamics sim- ulations sampling the conformational space of the biomolecule of interest. Using molecular dynamics simulations, the remarkable stable water-soluble-binding-protein is examined first. On a theoretical ba- sis, structural modifications that can influence the stability of the protein are discussed. Additionally, by combining the simulations with a QM/MM optimization scheme and quantum chemical calculations, spectroscopical properties can be investigated.
Markov State Models are applied frequently to capture the slow dynamics within simulation trajectories. They are based on a discretization of the conformational space. This discretization, however, introduces an error in the outcome of the analysis. The application of a core-set discretization can reduce this error. In this thesis, it is discussed how density-based cluster algorithms can be used to determine these core sets, and the application on linear and cyclic peptides is highlighted. The performance of a promising cluster algorithm is investigated and error sources in the construction of the Markov models are discussed. Finally, it is shown how molecular docking combined with molecular dynamics simulations can be used to determine the binding behavior of ligands towards biomolecules. In this context, the important in- teractions within the active site of an enzyme, and different binding modes of DNA intercalators are identified.
en
dc.format.extent
XIII, 298 Seiten
dc.rights.uri
http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen
dc.subject
Density-based Clustering
en
dc.subject
Core-set Markov State Models
en
dc.subject
Molecular Dynamics Simulations
en
dc.subject
Molecular Docking
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften
dc.title
Theoretical Analysis of Biomolecular Systems: Computational Simulations, Core-set Markov State Models, Clustering, Molecular Docking
dc.contributor.gender
male
dc.contributor.firstReferee
Keller, Bettina G.
dc.contributor.furtherReferee
Götze, Jan P.
dc.date.accepted
2020-02-03
dc.identifier.urn
urn:nbn:de:kobv:188-refubium-26738-2
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.note.author
The research presented in Section 3.1 is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in J. Phys. Chem. B, copyright © American Chemical Society after peer review. To access the final edited and published work see: Lemke, O.; Götze, J.P. „On the Stability of the Water-Soluble Chlorophyll-Binding Protein (WSCP) Studied by Molecular Dynamics Simulations“, J. Phys. Chem. B. 2019, 123 (50), 10594-10604, DOI: 10.1021/acs.jpcb.9b07915 (https://doi.org/10.1021/acs.jpcb.9b07915).
It is clearly stated that the in the PDF included unedited version is part of the dissertation. The edited published version is not part of the dissertation since the manuscript was accepted after the submission of this dissertation.
dcterms.accessRights.dnb
free
dcterms.accessRights.openaire
open access